Profile of Jennifer Lippincott-Schwartz, Ph.D.
Anything Can Work
Controversy is part of the scientific process. We all would be less knowledgeable without it. In my own research, it has forced me to be more innovative and to constantly dream up new approaches. It has also made me much more cautious about drawing firm conclusions before a given idea is thoroughly tested. That is all positive. The downside is the added pressure.
When I first proposed that components of the Golgi apparatus are in a steady-state system of assembly and disassembly, there was a lot of skepticism toward the idea. But it pushed me to incorporate green fluorescent protein (GFP) and other technologies to our work. For example, we were able to mark GFP-labeled membrane proteins in living cells using photoactivation or photobleaching, watch the proteins redistribute, and determine how fast they were moving. We were the first to introduce these kinds of approaches to membrane research.
New technologies drive the research in my lab. The view is that anything can work. I am incredibly optimistic. Although I have to admit, when we were first developing photoactivatable GFP, I doubted that the technique would succeed. One of my post-docs, George Patterson, had the idea for doing it. Because I had faith in him I said, “Let's give it a shot.” It was an incredible feeling when it did work.
My work on the Golgi apparatus started somewhat by chance. As a postdoc in Richard Klausner's lab at the National Institutes of Health, I identified a non-lysosomal pathway for the degradation of proteins in the endoplasmic reticulum (ER). To further pursue this pathway, I got a hold of the antibiotic brefeldin A to block the transport of proteins out of the ER. But to my complete shock, I saw that the Golgi structure was lost when I added the drug to cells. No one before had shown that an organelle could disappear. And we found that it was not just breaking apart, but rather proteins associated with the Golgi apparatus were redistributing into the ER. That finding made me stop working on the ER degradative pathway and start thinking about the dynamics and biology of eukaryotic organelles.
Today, I have people in the lab working on almost every organelle, including ER, peroxisomes, mitochondria, autophagosomes, in addition to the Golgi. I am fascinated with the global principles that guide organelle organization in cells. Our goal is to make sure that our basic understanding of these structures, so much of which has come from static images, can be reinforced by modern approaches. Thus, we are revisiting basic questions using the latest imaging techniques in living cells.
A consequence of this strategy is that it sometimes leads to new and controversial ideas. For example, although most people now accept that the Golgi exists as a steady-state system in interphase, there is still debate about how this organelle disassembles during cell division. Our view is that the mitotic breakdown of the Golgi apparatus results from Golgi proteins and membrane components being recycled back to the ER and retained in the ER or at ER exit sites. Those who oppose this model argue that the Golgi directly breaks down into small pieces that spontaneously come together at the end of mitosis. These two views—once further articulated—may not be too far apart, and the discrepancies may soon be resolved.
My father is partly responsible for my love for research. He was a physical chemistry professor at the University of Maryland, and through his work, I soon became aware of the mystery and excitement surrounding science. But after graduating from Swarth-more College in 1974, I was in no way ready to commit to graduate school. I had not experienced anything other than academics and knew nothing outside our modern western society. I wanted to see a different part of the world. I ended up teaching science in a bush school in Kenya for two years.
When I returned to the States, I taught high school physics and chemistry in California. The experience made me realize I wanted to do science. I therefore enrolled in a Masters program in biology at Stanford University, while my husband completed his law degree there. I then did my Ph.D. at the Johns Hopkins University with Doug Fambrough at the Carnegie Institution of Washington. That environment had a huge impact on my development as a biologist. It was a very unique place, and I was in awe of everyone around me. Every time I would do an experiment, I had five people from five different groups to talk to. I did not realize how special that was until I moved to other places.
